Efetividade da metilprednisolona na fase aguda do trauma raquimedular: revisão sistemática dos ensaios clínicos randomizados

Original

Article

effectiveness Of MethylpRednisOlOne in acute spinal cORd injuRy – a systeMatic Review Of RandOMized cOntROlled tRials RicaRdO vieiRa bOtelhO1*, jeffeRsOn walteR daniel2, jOsé luis ROMeO bOulOsa3, benedictO OscaR cOlli4, ROnald de lucena faRias5, OsMaR jOsé santOs MORaes6, wilsOn elOy piMenta jR.7, caRlOs henRique RibeiRO8, fRanciscO RicaRdO bORges RibeiRO9, MaRiO augustO taRiccO10, MaRciO vinhal de caRvalhO11, wandeRley MaRques beRnaRdO12 Association (Guidelines Project) and Congresso de Cirurgia Espinhal.

AbstrACt Steroid therapy has been tested as a neuronal protector in spinal cord injury. Multicenter studies published. Objective MethOds. Results. *Correspondence: Rua Haberbeck Brandão, nº 68 - apt 92 - Indianópolis Tel.: (11) 8111-8157-Fax: (11) 3276-2964 São Paulo, SP, Brazil CEP: 4027040

cOnclusiOn

Key

words:

i ntROductiOn

at reducing secondar y injuries, being considered as a -

Steroid therapy has been tested as a neuronal protector

Ribeirão Preto, SP

Paulo, SP

Rev Assoc Med Bras 2009; 2010; 56(6): 729-37

729

Botelho RV

et al

1

1985. 2 and specificity filters of PubMed Clinical Queries tool and studies suggested that the dosage in neuroprotective steroid therapy should be higher than that used until that 2

then designed. 3,4 1) Effect of MP on sCI-associated neurological damage search tool: Clinical Queries: largely spread even before their initial publica-

trial [Publication Type] OR controlled [Title/Abstract]

trial [Title/Abstract]))

5

Several critical studies regarding MP use have then

search tool: MesH browser: [Mesh]

OR

countries. 6,7,8,9,10,11 controlled trial as Topic

O bjectives -

2) Complications of MP therapy Search tools: Clinical Queries

and

MeSH

af ter spinal fracture?

M ethOds -

b) LILACs database: search:

-

C) EMbAsE database: search: 1)

-

PICO (P- Patients; I-

the inclusion criteria related to populations, inter ventions types of participants: Patients that suffered spinal

.

types of intervention:

types of outcomes studied:

Conflict of interest study designs included:

Critical appraisal and selection of studies -

12

assigns one

the literature search. Databases searched: reference review:

search strategy A) MEDLINE database:

730

Rev Assoc Med Bras 2010; 56(6): 729-37

effectiVeness

of methylpRednisolone in acute spinal coRd injuRy

–a

systematic ReView of Randomized contRolled tRials

38

and one secondar y analysis. 39 1,2,3,4,40,41,42,43,44, 45

retrizes.org.br/projeto_diretrizes/texto_introdutorio.pdf);

reanalysis: Evidence retrieved from PubMed – 2nd quality analysis of articles – Critical appraisal of selected evidence Articles excluded by PICO: The ar ticles by Bracken et al. published in 1984 1 and in 1985 2

drug-addicted persons, individuals using cor ticoids for The ar ticles by Petitjean et al. 43 and Pointillar t et al. 41 can be considered superposable, since they describe the allocation; blinding of raters; therapy protocol consisting 42

did not use placebo as an inter-

The ar ticle by Epstein et al. 45 -

studies included with a Jadad score greater than three: and the sensor y score related to pinprick-evoked pain and neurological improvement six 3 ) and one 4

3

describing the results af ter one year. 4

and risks.

-

R esults

-

The three search strategies uncovered 72 scientific inclusion and exclusion criteria and to study design. 1) Effect of MP on sCI-associated neurological damage Evidence retrieved from PubMed – 1st quality analysis of published articles – selection by study design 5,6,8,10,13,15,16,17,18,20 taries and discussion, 7,9,11,19,21,23,24,25,26,27,28,29,30 29,30 three studies on the use of GM-1 ganglioside, 33,34,35 one ar ticle analyzing the role of surger y in neurological recover y, 17

Rev Assoc Med Bras 2009; 2010; 56(6): 729-37

2) studies on complications of MP therapy Evidence retrieved – 1st quality analysis of articles – selection according to type of publication The ar ticles by Bracken 1984, 1 1991, 30 and 1993 26

731

Botelho RV

et al

did not use a placebo control group 1 ar ticles by Petitjean et al., 43 Bracken 1997, 44 Pointillar t et al., 40 and Bracken 1998 42 placebo, being, therefore, excluded. The study by Epstein et al. 45 excluded. Evidence retrieved – 2nd quality analysis of published articles

40

had not been analyzed in the

sensor y changes did not reach the significance level set for

Analysis of motor improvement after six weeks: (185/487).

3,4

al. 40 40

-

Evidence retrieved from LILACs – 1st quality analysis of published articles – selection by study design LILACS database search returned nine ar ticles: six

Analysis of motor improvement after six months:

46,47,48,49,50,51

study, 55 one case series analysis, 53 and one case repor t. 54 study. Evidence retrieved from EMbAsE – 1st quality analysis of published articles – selection by study design EMBASE database search returned 16 ar ticles, in

ence of 4.5 points. Analysis of motor improvement after one year:

study by Cengiz 55 56,57,58,61,60,61,6 2,63,64,65,66,67,68

the study by Pettersson 69 70

conference paper.

R esults

function, pinprick response, and touch sensation). Of the total patients in the initial group receiving MP and

1) Effect of MP on sCI-associated neurological damage A) results for motor function The difference in the final neurological status of the MP

b) results for sensory function

eight hours of injur y.

732

Rev Assoc Med Bras 2010; 56(6): 729-37

effectiVeness

of methylpRednisolone in acute spinal coRd injuRy

–a

systematic ReView of Randomized contRolled tRials

table 1. Motor scores at baseline, improvement obtained and final score six weeks, six months and one year after injury in the methylprednisolone (MP) and placebo (PL) groups Period of follow-up

MP

PL

Difference

2

Motor score at baseline*

Final score***

p=0.78

Motor score at baseline*

Final score***

p=0.67

Motor score at baseline*

One year

Final score***

p=0.52

table 2. Improvement in pain appreciation (pinprick) and superficial sensation (light touch) scores between groups six months after injury PINPrICK Groups

Methylprednisolone (MP)

Placebo (PL)

Score at baseline*

Difference

2

1.4 12.9

(points)**

5.9

7

Final score

p= 0.59

tOUCH Groups

Methylprednisolone (MP)

Placebo (PL)

Score at baseline* (points)** Final score

Rev Assoc Med Bras 2009; 2010; 56(6): 729-37

Difference

2

1.4 9.8

4.6

5.2 p=0.71

733

Botelho RV

et al

table 3. Improvement in pain appreciation (pinprick) and superficial sensation (light touch) scores between groups one year after injury PINPrICK Groups

Methylprednisolone (MP)

Score at baseline* (points)**

10.8

Final score

Placebo (PL)

Difference

52.6

1.3

8.4

2.4

2

61

p= 0.84

tOUCH Groups

Methylprednisolone (MP)

Placebo (PL)

Difference

Score at baseline* (points)**

2

1.7 9.4

6.0

3.4

Final score

p=0.90 2

eight BCP cases in the MP group and one case in the PL

four cases in the MP group and none in the PL group (odds difference in final sensor y scores for pain appreciation Regarding super ficial sensation (light touch), the differ-

d iscussiOn

points, respectively.

Critical appraisal studies using a placebo control group: Although there is substantial literature on MP use,

2) results- studies on complications of MP therapy: NAsCIs II 3

-

year af ter injur y. 3,4 . The studies by Pointillar t et al. 41 and Petitjean et al. 43

-

different languages and being, therefore, considered as one single study. The study by Pointillar t et al. 41 did not

study by Matsumoto et al.:

734

40

Rev Assoc Med Bras 2010; 56(6): 729-37

effectiVeness

of methylpRednisolone in acute spinal coRd injuRy

–a

report of results in NAsCIs II:

systematic ReView of Randomized contRolled tRials

Analysis model used in the present review:

3

-

real clinical benefits of MP therapy: -

40

70 points. -

c OnclusiOn subgroup analysis: Findings based on subgroup analyses should not

the results do not suggest clinical benefits.

did not provide the results as absolute data, hindering recalculation of risk increase or decrease and of the neces-

patients aged about 60 years.

Definition of the amount of clinically significant improvement:

s uMMaRy

Of evidence

The differences between motor and sensory final scores of patients in the MP and PL groups were not significant and were minimal in relation to the maximum normal score possible, thus failing to suggest clinical benefits. In addition, the use of MP may be associated with an increased risk of pulmonary complications and gastrointestinal bleeding.

size calculation yields the possibility of producing results

f inancial s uppORt : functional independence scale that could reveal

Cirurgia Espinhal. Conflict of interest: concerning the publication of this ar ticle.

real benefit of the increase of 2.5 points in the final cally insignificant.

R efeRences

DF, et al. Methylprednisolone and neurological function 1 year af ter

-

Rev Assoc Med Bras 2009; 2010; 56(6): 729-37

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Botelho RV

et al

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